metastatic PCs with elevated TERT expression and using wholegenomesequencing (WGS) identified genomic rearrangements that led to super-enhancer positioning proximal to the TERT promoter in two tumors.
Materials and methods
Patients and samples

Hidewaki Nakagawa

a number of cancer genomes. GWAS, whole-genomesequencing (WGS), whole exome sequencing (WES), and RNA sequencing (RNA-Seq) have now been conducted for many types of cancer genomes worldwide, including the International Cancer Genome Consortium (ICGC

Tirtha K Das and Ross L Cagan

Twenty-five years ago, RET was identified as the primary driver of multiple endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all shown limited success, and none of these approaches have proven durable in advanced disease. Non-mammalian models that incorporate the oncogenic RET isoforms associated with MEN2 and other RET-associated diseases have been useful in delineating mechanisms underlying disease progression. These models have also identified novel targeted therapies as single agents and as combinations. These studies highlight the importance of modeling disease in the context of the whole animal, accounting for the complex interplay between tumor and normal cells in controlling disease progression as well as response to therapy. With convenient access to whole genome sequencing data from expanded thyroid cancer patient cohorts, non-mammalian models will become more complex, sophisticated and continue to complement future mammalian studies. In this review, we explore the contributions of non-mammalian models to our understanding of thyroid cancer including MTC, with a focus on Danio rerio and Drosophila melanogaster (fish and fly) models.

sequencing (Applied Biosystems) was employed to sequence the reaction products, and the samples were run on an ABI Prism 3130xl – Genetic Analyzer (Applied Biosystems). Whole-exome and whole-genomesequencing Whole-exome sequence data were generated using

Jamie L Van Etten and Scott M Dehm

has provided evidence that primary tumors exhibit multiclonality coincident with multifocal disease. For example, whole-genomesequencing (WGS) in a cohort of five patients (Gleason scores 7–8) who underwent radical prostatectomies provided the first

involved in metabolic switches. Possibly additional tumor drivers need to be identified. Indeed, we only found a PTEN- and a TP53 -inactivating gene variant after whole-genomesequencing (WGS) of three FTC-OV with NHG (data not shown). Thus, FTC-OV does